Improving the Safety of Oral Immunotherapy for Cow's Milk Allergy

NCT02216175 | Completed DMC

• 2 other identifiers: 18SM456918/LO/1070
• Study Type: interventional
• Target: 68
• Locations: 2 countries
• Sites: 2

Brief Summary

Allergy to cow's milk is the most common food allergy affecting children. There is currently no accepted routine clinical therapy to cure milk allergy. Recently studies have attempted to induce desensitisation using small daily doses of cow's milk, predominantly by the oral route (oral immunotherapy, OIT). Although this therapy works for some people, its effects are not generally long lasting and it is associated with significant side effects during protocol, including potentially life-threatening allergic reactions. Pilot data suggests that sublingual immunotherapy (SLIT, where allergen is held under the tongue, rather than swallowed) can also induce a degree of desensitisation, but with fewer adverse events. However, the degree of desensitisation induced appears to be lower than that with oral immunotherapy. The investigators wish to determine whether a sublingual pretreatment phase can improve the safety of conventional OIT in cow's milk allergy.

Conditions

Food Allergy

Keywords

Cow's milk allergy; Desensitisation; Safety

Outcome Measures

Primary Outcomes (1)

• Adverse events in participants

  Proportion of participants experiencing adverse events (excluding mild, non-transient symptoms) conventional OIT to cow's milk in phase 2, in those who have received SLIT pretreatment compared to placebo.

  1 year

Secondary Outcomes (10)

• Incidence of adverse events

  1 year

• Eliciting dose(mg cow's milk protein) at DBPCFC after each phase of immunotherapy

  1 year

• Change in Health-related quality of life (HRQL) from baseline - assessed using FAQLQ - after each phase of immunotherapy

  15 months

• Change in Health-related quality of life (HRQL) from baseline - assessed using FAIM - after each phase of immunotherapy

  15 months

• Change in Health-related quality of life (HRQL) from baseline - assessed using Change in EQ-5D from baseline - after each phase of immunotherapy

  15 months

Study Arms (3)

SLIT followed by Conventional OIT

EXPERIMENTAL

Participants will receive up to 7 months of SLIT followed by 6 months conventional OIT to cow's milk

Other: SLIT to cow's milk; Other: Conventional OIT to cow's milk

Conventional OIT

ACTIVE COMPARATOR

Participants will receive up to 7 months of low dose OIT, followed by 6 months conventional OIT to cow's milk

Other: Low dose OIT; Other: Conventional OIT to cow's milk

Delayed start OIT

PLACEBO COMPARATOR

Participants will receive up to 7 months placebo, followed by 6 months conventional OIT to cow's milk

Other: Conventional OIT to cow's milk

Interventions

SLIT to cow's milk OTHER

Sublingual immunotherapy

SLIT followed by Conventional OIT

Low dose OIT OTHER

Oral Immunotherapy (low dose)

Conventional OIT

Conventional OIT to cow's milk OTHER

Oral Immunotherapy

Conventional OIT; Delayed start OIT; SLIT followed by Conventional OIT

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Allergic to 1.44g CM protein (approx. 40ml fresh milk) or less, at DBPCFC prior to randomisation
• Informed consent of parent/legal guardian, patient assent where possible

You may not qualify if:

• Required previous admission to an intensive care unit for management of an allergic reaction.
• Significant symptoms of non---IgE---mediated CM allergy within the previous 12 months.
• Children with a past history of CM allergy currently consuming CM-containing products other than extensively--heated milk in baked foods (e.g. biscuits, cakes).
• Poorly controlled asthma within the previous 3 months (as defined by clinician judgement with reference to the ICON consensus), or asthma requiring treatment with \>5 days oral corticosteroids within the previous 3 months.
• Clinically significant chronic illness (other than asthma, rhinitis or eczema)
• History of symptoms of eosinophilic oesophagitis, irrespective of cause
• Undergoing specific immunotherapy to another allergen and within the first year of treatment.
• Receiving anti--IgE therapy, oral immunosuppressants, beta---blocker or ACE inhibitor.
• Pregnancy
• Unwilling or unable to fulfil study requirements

Sponsors & Collaborators

• Imperial College London: lead
• JP Moulton Charitable Foundation: collaborator
• Sociedad Española de Alergología e Inmunología: collaborator
• Sociedad Española de Inmunología Clínica, Alergología y Asma Pediátrica: collaborator

Study Sites (2)

Niño Jesús Hospital

Madrid, Spain

Location

Imperial College London / Imperial College Healthcare NHS Trust

London, United Kingdom

Location

Related Publications (1)

• Turner PJ, Duca B, Chastell SA, Alvarez O, Bazire R, Vazquez-Ortiz M, Rodriguez Del Rio P. IgE-sensitization predicts threshold but not anaphylaxis during oral food challenges to cow's milk. Allergy. 2022 Apr;77(4):1291-1293. doi: 10.1111/all.15195. Epub 2021 Dec 14. No abstract available.

  PMID: 34874567 DERIVED

MeSH Terms

Conditions

Food Hypersensitivity; Milk Hypersensitivity

Condition Hierarchy (Ancestors)

Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MRC Clinician Scientist, Clinical Senior Lecturer and Hon Consultant in Paediatric Allergy & Immunology

Study Record Dates

• First Submitted: August 7, 2014
• First Posted: August 13, 2014
• Study Start: July 19, 2018
• Primary Completion: September 30, 2021
• Study Completion: January 19, 2022
• Last Updated: January 18, 2023

Record last verified: 2023-01

Locations

GB (1); ES (1)